AstraZeneca Submits IND Applications in China for Two Potential First-in-Class Oncology Candidates: Oleclumab and Monalizumab

Source: Medicinal Observer

On January 7, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) disclosed that AstraZeneca simultaneously submitted clinical trial applications for two Class 1 new drugs, which have been accepted. They are: the anti-CD73 antibody oleclumab, and the anti-NKG2A antibody monalizumab. Both CD73 and NKG2A are emerging targets in cancer immunotherapy.

Screenshot source: CDE official website

According to publicly available information from AstraZeneca, oleclumab is a potential "first-in-class" anti-CD73 monoclonal antibody that selectively binds to and inhibits the activity of CD73. Oleclumab is currently in phase 2 clinical trials for various malignant tumors.

CD73 is the rate-limiting enzyme that catalyzes the conversion of adenosine monophosphate (AMP) to adenosine. It is widely expressed on stromal endothelial cells and tumor cell surfaces, hydrolyzing AMP in the environment by removing phosphate groups, thereby generating a large number of immunosuppressive adenosine molecules within the tumor microenvironment. Given the critical role of CD73 in tumor growth and metastasis, it has become one of the leading targets in the field of cancer immunotherapy.

Another product, monalizumab, is a potential "first-in-class" anti-NKG2A antibody co-developed by AstraZeneca and Innate Pharma. It has extremely high specificity for human NKG2A. In in vitro experiments, this antibody demonstrated the expected effects, effectively enhancing the anti-tumor capabilities of T cells and natural killer cells. Currently, the product is undergoing a Phase 3 clinical trial named INTERLINK-1 to evaluate the efficacy of monalizumab combined with cetuximab in treating patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have received prior treatment.

NKG2A is considered a promising immune checkpoint inhibitor target. It is highly expressed on the surface of T cells and natural killer cells (NK cells), and the binding of NKG2A to its ligand inhibits the function of T cells and natural killer cells. Studies have shown that blocking the binding of NKG2A to its ligand has the potential to unleash the activity of immune cells.

At the 2021 European Society for Medical Oncology (ESMO) Congress, AstraZeneca presented the efficacy and safety of the anti-PD-L1 antibody Imfinzi as a monotherapy or in combination with oleclumab or monalizumab for the treatment of patients with locally advanced, unresectable stage III non-small cell lung cancer whose disease had not progressed after chemoradiotherapy.

This interim analysis of the Phase 2 clinical trial showed that at a median follow-up time of 11.5 months, compared with Imfinzi monotherapy, the combination of Imfinzi and oleclumab reduced the risk of disease progression or death by 56%; the combination of Imfinzi and monalizumab reduced the risk of disease progression or death by 35%. The progression-free survival rates at 10 months for the three groups were: Imfinzi + oleclumab (64.8%), Imfinzi + monalizumab (72.7%), and Imfinzi monotherapy (39.2%).

Note: The original text has been abridged.

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